1. Field of the Invention
The present invention concerns a new isolated and purified strain of virulent, hemorrhagic feline calicivirus, vaccines produced therefrom and the use of the vaccines to protect cats from calicivirus infection or disease.
2. Description of the Related Art
All patents and publications cited in this specification are hereby incorporated by reference thereto in their entirety.
Feline calicivirus (FCV) often causes an acute crisis in multiple-cat environments, particularly animal hospitals and, to a lesser extent, animal shelters. Typically, the FCV infection presents signs resembling viral rhinotracheitis (FVR) by affecting the upper respiratory tract and, on occasion, producing joint pain and lameness. Additionally, the infected cat will develop ulcers on the tongue and in the mouth region. Vesicles and erosions of the nasal passages, the hard palate and the tongue appear prevalent. Other symptoms of FCV disease include high fever, hair loss, skin ulcerations and edema (swelling) in the legs or around the face. Depending on the virulence of the infecting strain, the FCV infection may become fatal. The primary method of transmission is through the oral route of infection but cats can also get the infection from inhalation of infectious virus found in the saliva, feces or urine of infected cats.
The FCV infection can affect both domestic cats and some wild feline species. Since FVR and FCV comprise almost 90% of all feline respiratory infections, the availability of effective vaccines to prevent these two diseases is of great significance. FCV is a single-stranded RNA virus capable of mutating into new strains (J. N. Burroughs et al., “Physio-chemical evidence for the re-classification of the caliciviruses,” Journal Gen. Virol. 22:281-286 (1974)). Over sixty-five feline caliciviruses exist worldwide, which makes adequate protection by vaccination using a singly comprised vaccine largely incomplete and difficult. Because the virus is capable of mutation, monovalent vaccines based on a single strain of FCV may not be sufficiently protective against other FCV strains (see, generally, N. C. Pedersen et al., “Mechanisms for persistence of acute and chronic feline calicivirus infections in the face of vaccination,” Veterinary Microbiol. 47(1-2):141-156 (November 1995); A. Lauritzen et al., “Serological analysis of feline calicivirus isolates from the United States and United Kingdom,” Veterinary Microbiol. 56(1-2):55-63 (May 1997); T. Hohdatsu et al., “Neutralizing feature of commercially available feline calicivirus (FCV) vaccine immune sera against FCV field isolates,” Journal of Veterinary Medicine Sci., 61(3):299-301 (March 1999); A. D. Radford et al., “Comparison of serological and sequence-based methods for typing feline calicivirus isolates from vaccine failures,” Vet. Rec. 146(5): 117-123 (Jan. 29, 2000)).
Another problem with FCV is that the virus is highly contagious, infected cats will continue to shed the virus for long periods of time after infection and recovered cats may remain lifelong carriers of the infectious virus. Asymptomatic cats can even spread fatal disease to other healthy cats. Recent outbreaks have been reported in Northern California and New England of two genetically diverse strains of highly virulent, hemorrhagic calicivirus that were particularly fatal to the feline population in animal shelters, named FCV-Ari and FCV-Diva, respectively (N. C. Pedersen et al., “An isolated epizootic of hemorrhagic-like fever in cats caused by a novel and highly virulent strain of feline calicivirus,” Veterinary Microbiol. 73:281-300 (May 2000); E. M. Schorr-Evans et al., An epizootic of highly virulent feline calicivirus disease in a hospital setting in New England,” Journal of Feline Medicine and Surgery 5:217-226 (2003)).
In the past, monovalent viral vaccines have been described and several manufactured to prevent feline diseases using a variety of antigens such as the feline calicivirus F9 strain (U.S. Pat. No. 3,944,469 (J. L. Bittle et al.)), feline Chlamydia psittaci (U.S. Pat. No. 5,972,350 (R. A. Atherton et al.) and U.S. Pat. No. 5,242,686 (H.-J. Chu et al.)), feline leukemia virus (U.S. Pat. No. 4,264,587 (N. C. Pedersen et al.)) and the like. Other calicivirus strains such as the FCV-M8 and FCV-255 and feline rhinotracheitis virus have also been previously isolated and described for vaccine use (E. V. Davis et al., “Studies on the safety and efficacy of an intranasal feline rhinotracheitis-calici virus vaccine,” VM-SAC 71:1405-1410 (1976); D. E. Kahn et al., “Induction of immunity to feline caliciviral disease,” Infect. Immun. 11:1003-1009 (1975); D. E. Kahn, “Feline viruses: pathogenesis of picornavirus infection in the cat,” Am. J. Vet. Research 32:521-531 (1971)). Further, U.S. Pat. No. 4,522,810 (N. C. Pedersen) describes a feline calicivirus vaccine that contains the FCV-2280 strain. U.S. Pat. No. 6,231,863 (D. Colau et al.) describes nucleotide sequences from the genome of the FCV-2280 strain and vaccines using the nucleotide sequences of the capsid gene for preventing feline calicivirus disease. U.S. Pat. No. 5,106,619 (G. P. Wiesehahn et al.) discloses the preparation of inactivated viral vaccines that include feline calicivirus among others. U.S. Pat. No. 6,051,239 (L. Simpson et al.) describes oral vaccines that use a modified botulinum toxin in conjunction with antigens such as the calicivirus.
More recently, a strain of FCV-Kaos was identified (K. F. Hurley et al, “An Outbreak of virulent systemic feline calicivirus disease, J. Am. Vet. Med. Assoc. 224(2):241-249 (Jan. 15, 2004)) and, subsequently, both FCV-Kaos and FCV-Ari strains were isolated (U.S. Patent Application No. 20040180064 A1, Hemorrhagic feline calicivirus, pub. Sep. 16, 2004). The isolated virulent systemic calicivirus (VS-FCV) strains, including FCV-Kaos, FCV-Ari and FCV-Bellingham, have been described as comprising a capsid protein including an amino acid residue selected from the group consisting of lysine (K) at amino acid position 448; glutamic acid (E) at amino acid position 452; lysine (K) at amino acid position 581; and aspartic acid (D) at amino acid position 581 (U.S. Patent Application No. 20040259225 A1, Virulent systemic feline calicivirus, pub. Dec. 23, 2004).
Multivalent vaccines have been prepared or described to contain mixtures of many viral antigens such as Chlamydophila felis (formerly known as feline Chlamydia psittaci) in combination with one or more pathogens comprising feline leukemia virus, feline panleukopenia virus, feline calicivirus, feline rhinotracheitis virus, feline acquired immunodeficiency virus, rabies, feline infectious peritonitis, Borrelia burgdorferi and the like (U.S. Pat. No. 6,004,563 (H.-J. Chu et al.)). Another mixture of Rickard isolate feline leukemia virus, feline rhinotracheitis virus, feline calicivirus and feline panleukemia virus has similarly been disclosed as a vaccine (U.S. Pat. No. 5,374,424 (W. H. Kelsey et al.)).
Unfortunately, none of the prior vaccines that contain previously used strains of the feline calicivirus adequately protect the feline from the emerging hemorrhagic feline calicivirus strains. In the recent hemorrhagic feline calicivirus outbreaks, there were a significant number of deaths despite the fact that the cats had received vaccinations against the calicivirus.
As a consequence, there is a definite art-recognized need in the veterinary field to produce an efficacious, safe vaccine against the highly virulent, hemorrhagic feline calicivirus infections. Another art-recognized need is to provide a broad-spectrum viral vaccine that protects cats against serious infection and disease caused by both hemorrrhagic and common FCV strains. The novel FCV strain of the present invention is able to satisfy those needs by uniquely and advantageously eliciting specific immune response against the virulent, hemorrhagic strain of FCV to protect cats from acute and chronic viral disease. In combination with common calicivirus strains, the new FCV strain of this invention is able to achieve excellent virus-neutralizing antibody titers and make broad-spectrum immunization possible.